crossing96/oncoscreening huggingface dataset:
Retinoblastoma protein expression predicts response to bacillus Calmette-Guérin immunotherapy in patients with T1G3 bladder cancer.	OBJECTIVES: Bacillus Calmette-Guérin (BCG) immunotherapy is regarded as the current treatment of choice for stage T1 grade 3 (T1G3) bladder cancer (BC), though its efficacy is limited by high recurrence and progression rate. Identification of molecular prognosticators that might be helpful in discriminating between responders and nonresponders to BCG treatment is therefore of major clinical importance; thus we focused on the cell-cycle related retinoblastoma protein (pRB), which had been already investigated in bladder cancer. The goal of our study was specifically to address whether its expression predicts the outcomes of BCG treatment for patients with T1G3 disease. MATERIALS AND METHODS: To address this issue, paraffin-embedded specimens of 27 patients having undergone transurethral resection of T1G3 BC and intravesical instillations of BCG (induction + 1 year maintenance) were immunostained with pRB monoclonal antibody. Patients in whom the bladder muscle was not clearly visible, and healthy, as well as patients with TaG3 tumors or with concomitant carcinoma in situ were excluded. Mean follow-up was 60 months (range 15-135). RESULTS: Thirteen tumors showed normal (1% to 50% labeling index) while 14 showed altered pRB expression, consisting of no expression (0% labeling index) in six and overexpression (>50% labeling index) in eight. Recurrence occurred in 10 (37%) patients and mean time to recurrence was 22.8 months (range 6-48). Recurrence rate was 57% in patients with altered and 15% in those with normal pRB expression, with a statistically significant difference in disease-free survival (P = 0.037). Progression occurred in five (18.5%) patients and mean time to progression was 24 months (range 6-48). Progression rate was 36% in patients with altered and 0% in patients with normal pRB expression, with a statistically significant difference in progression-free survival (P = 0.018). CONCLUSIONS: In this homogeneous population of T1G3 bladder tumors, altered pRB expression predicted recurrence and progression after BCG treatment. These findings outline the potential role of pRB immunostaining in predicting T1G3 BC response to BCG immunotherapy.	bladder
[Case of tuberculous epididymitis caused by intravesical BCG therapy].	Intravesical Bacillus Calmette-Guerin (BCG) therapy is commonly used against superficial urothelial carcinoma, especially carcinoma in situ (CIS). We report a case of tuberculous epididymitis that occurred during a course of intravesical BCG therapy. A 76-year-old man had received intravesical BCG therapy for multiple superficial bladder cancer and CIS in prostatic urethra after transurethral resection of bladder tumor (TUR-Bt). He recognized hard nodules in the left scrotum after 4 times intravesical BCG therapy. Skin fistula in scrotum occurred 5 months later. We performed left orchiectomy with scrotum skin resection. Histological diagnosis was tuberculous epididymitis. Postoperatively, he was administered chemotherapy consisting of isoniazid, refampin and ethambutol.	bladder
Polyoma virus infection and urothelial carcinoma of the bladder following renal transplantation.	Renal transplant recipients are at increased risk of bladder carcinoma. The aetiology is unknown but a polyoma virus (PV), BK virus (BKV), may play a role; urinary reactivation of this virus is common post-renal transplantation and PV large T-antigen (T-Ag) has transforming activity. In this study, we investigate the potential role of BKV in post-transplant urothelial carcinoma by immunostaining tumour tissue for PV T-Ag. There was no positivity for PV T-Ag in urothelial carcinomas from 20 non-transplant patients. Since 1990, 10 transplant recipients in our unit have developed urothelial carcinoma, and tumour tissue was available in eight recipients. Two patients were transplanted since the first case of PV nephropathy (PVN) was diagnosed in our unit in 2000 and both showed PV reactivation post-transplantation. In one of these patients, there was strong nuclear staining for PV T-Ag in tumour cells, with no staining of non-neoplastic urothelium. We conclude that PV infection is not associated with urothelial carcinoma in non-transplant patients, and is uncommon in transplant-associated tumours. Its presence in all tumour cells in one patient transplanted in the PVN era might suggest a possible role in tumorigenesis in that case.	bladder
Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin.	PURPOSE: We studied the safety and preliminary efficacy (marker tumor ablation) of 5 doses of BC-819 given as 6 intravesical infusions in patients with superficial bladder cancer in whom intravesical therapy with bacillus Calmette-Guerin had failed. BC-819 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin. MATERIALS AND METHODS: A total of 18 patients in 4 groups of 3 and 1 group of 6 received escalating doses of BC-819 intravesically during 7 weeks. Patients had low grade superficial bladder cancer, which expressed H19. The effect on a marker tumor was examined 12 weeks after starting treatment. The escalating doses were 2, 4, 6, 12 and 20 mg plasmid per intravesical treatment. Responders continued to receive BC-819 once monthly every month for 1 year. RESULTS: No dose limiting toxicity was observed. The most frequent adverse events were mild to moderate bladder discomfort, dysuria, micturition urgency, urinary tract infection, diarrhea, hypertension and asthenia. Intravesical administration of BC-819 resulted in complete ablation of the marker tumor without any new tumors in 4 of the 18 patients for a 22% overall complete response rate. Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. Nine patients received monthly maintenance, of whom 4 and 1 were disease-free at 35 and 49 weeks, respectively. CONCLUSIONS: Intravesical BC-819 causes tumor ablation following intravesical administration at doses that were well tolerated. It is worthy of continued clinical investigation.	bladder
Outcome and quality of life in patients operated on with radical cystectomy and three different urinary diversion techniques.	OBJECTIVE: To assess outcome and quality of life (QoL) aspects among patients treated with three different diversion techniques: Bricker, Studer or Hemi-Kock, after radical cystectomy. MATERIAL AND METHODS: Thirty-seven patients with Bricker conduit, 19 with Studer neobladder and 16 with Hemi-Kock neobladder answered a questionnaire concerning QoL, general health, relationship with partner, sexual function, satisfaction with information and follow-up, etc. Response rates were 79% (37/47), 100% (18/18) and 86% (19/22), in Bricker, Studer and Hemi-Kock patients respectively. Medical records were reviewed to assess cancer type, grade and stage. RESULTS: Both Studer and Bricker patients reported a high mean value of QoL (p>0.05). QoL was not influenced by tumour stage (pTa-T2 versus pT3-4) (p>0.05). After surgery, more Studer patients (78%) experienced practical problems compared with Bricker patients (40%) (p=0.01). Studer patients reported a higher influence on the everyday life compared with Bricker and Hemi-Kock patients (p<0.01 and p=0.05, respectively). Leakage in day-time was reported by 53% of Studer patients and 16% of Hemi-Kock patients (p=0.03). Moreover, all Studer patients had leakage at night compared with 58% of Hemi-Kock (p<0.01). The follow-up time after surgery was 56 months for Hemi-Kock patients compared with 26 months for Studer patients. Erectile dysfunction was reported by 81% of the men, with no difference between the methods of diversion. CONCLUSIONS: Patients in all diversion groups rated their QoL as high. Type of urinary diversion was not associated with any statistically significant difference in QoL outcome. However, Studer patients reported less favourable outcome regarding urinary continence compared with Hemi-Kock patients, probably owing to factors as shorter follow-up and surgical skill and experience. The results regarding urinary continence may explain why Studer patients reported more practical problems and a higher influence on their everyday life than Bricker and Hemi-Kock patients.	bladder
Expression of the endothelin axis in noninvasive and superficially invasive bladder cancer: relation to clinicopathologic and molecular prognostic parameters.	BACKGROUND: The endothelin (ET) axis plays a role in cancer biology and plays a potential role as a target for molecular therapy in urogenital tumours. Alterations of several proteins of the ET axis were detected in invasive bladder cancer. OBJECTIVES: To examine the potential role of the expression of ET axis proteins compared to other prognostic parameters (kinase inhibitor 67 [Ki-67], tumour protein 53 [TP53], and fibroblast growth factor receptor 3 gene [FGFR3] mutations) in noninvasive and invasive bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: Tissue microarrays from 154 consecutive patients with pTa-pT2 urothelial bladder cancer were immunohistochemically stained for endothelin 1 (ET-1), endothelin A and B receptors (ET(A)R, ET(B)R), TP53, and Ki-67. FGFR3 mutations were detected by SNaPshot analysis. MEASUREMENTS: The results were correlated with clinicopathologic parameters and disease-specific survival, overall survival, and recurrence-free survival. RESULTS AND LIMITATIONS: Proteins of the ET axis were frequently expressed in bladder cancer (ET-1 in 62% of tumours, ET(A)R in 93% of tumours, and ET(B)R in 84% of tumours). ET-1 expression was strongly correlated with tumour stage (p=0.015), histologic grade (p=0.008), and low proliferation status (p=0.003). ET(A)R immunostaining was only associated with low proliferation status (p=0.015). Kaplan-Meier survival analysis showed a significantly longer overall survival for patients with ET-1-expressing tumours (p=0.007). A significantly longer disease-free survival was found in patients with ET(A)R-expressing tumours (p=0.040), whereas ET(B)R expression was significantly correlated to a longer disease-free survival only in subgroups of patients with multifocal tumours (p=0.031), low proliferation index (Ki-67 ≤10; p=0.050), low TP53 expression (≤10; p=0.018), and tumours with an FGFR3 mutation (p=0.026). In the global model for recurrence-free survival, only high-grade (p=0.048) and negative ET(A)R immunoreactivity (p=0.048) were correlated with poor prognosis. CONCLUSIONS: In addition to other factors, particularly age at diagnosis and growth pattern, lack of ET-1 expression may be an independent negative prognostic factor for the overall-survival probability of bladder cancer patients. Lack of ET(A)R expression may be an independent negative marker for recurrence-free survival.	bladder
Inflammatory pseudotumours of the urinary bladder in dogs resembling human myofibroblastic tumours: a report of eight cases and comparative pathology.	Eight cases of inflammatory myofibroblastic tumours (IMT) of the urinary bladder in dogs are described, including their clinical, imaging, morphological, and histopathological aspects. Old small breed female dogs were more commonly affected. Haematuria was the main clinical sign, often associated with dysuria and crystalluria. The IMT appeared as single or multiple, polypoid, firm masses, measuring 1-7 cm. Histologically, the masses were well delineated, covered by a benign hyperplastic urothelium and diffusely infiltrated by a mixed inflammatory component. The cells were spindle-shaped, adopting a fascicular, pallisading or whirling organisation and were vimentin and variably desmin and actin positive. The nuclei were globular, containing open chromatin and prominent nucleoli. Mild to moderate pleomorphism and little mitotic activity were present. These morphological features are compatible with human myofibroblastic inflammatory tumours.	bladder
Somatic mutations of adenomatous polyposis coli gene and nuclear b-catenin accumulation have prognostic significance in invasive urothelial carcinomas: evidence for Wnt pathway implication.	Wnt pathway signaling is crucial in many cancers and data indicate crosstalk with other key cancer pathways, however in urothelial carcinogenesis it has not been extensively studied. We searched for mutations in adenomatous polyposis coli (APC), a key regulator of the pathway, and studied b-catenin expression and interactions with the expression of other markers of apoptosis, angiogenesis, and proliferation in patients with invasive urothelial cancer. The mutation cluster region of APC was directly sequenced in 70 patients with muscle invasive disease who were treated with surgery and adjuvant chemotherapy. COX-2, p53, Ki67, and b-catenin were studied immunohistochemically and micro vessel density was quantified by CD105 expression. Single somatic amino-acid substitutions (missense) were found in 9 (13%) and frameshift deletions in 2 (3%) tumors, all located in regions adjacent to b-catenin binding sites. Patients having either APC missense mutations or b-catenin nuclear accumulation had less frequent COX-2 overexpression (24% vs. 76%, p = 0.043) and more frequent lymph node involvement (75% vs. 38%, p = 0.023). Patients with either APC mutations or b-catenin accumulation had shorter disease-free interval (13.4 vs. 28 months, p = 0.07), whereas in multivariate analysis they had shorter disease-specific survival (60.5 vs. 20.6 months, p = 0.048). Somatic APC missense mutations are not rare in advanced urothelial neoplasms. Either APC mutations and/or aberrant expression of b-catenin are associated with worse outcome. Further study of the role of the Wnt pathway, potential crosstalk with other pathways and potential candidate therapeutic targets in urothelial cancer is needed.	bladder
[Laparoscopic radical cystectomy for 43 patients with invasive bladder carcinoma].	OBJECTIVE: To report initial experience with laparoscopic radical cystectomy in 43 patients with invasive bladder carcinoma. METHODS: From December 2003 to October 2006, 29 men and 14 women underwent laparoscopic radical cystectomy with extracorporeal-assisted urinary diversion for transitional cell carcinoma of the bladder (n=40), adenocarcinoma (n=2) and squamous cell arcinoma (n=1). We report the specific technical details and present initial results of our series. RESULTS: The mean operative time of laparoscopic radical cystectomy with pelvic lymph node dissection was 195.4 min, the mean blood loss 273.7 ml, and the transfusion rate 6.9%. Two procedures converted to open techniques. Lymphadenectomy detected lymph node metastasis in three patients. CONCLUSIONS: We demonstrate that the combination of laparoscopic radical cystectomy and extracorporeal urinary diversion is possible and remains a safe, feasible, and repeatable surgical technique. The laparoscopic surgery with extracorporeal urinary reconstruction is emerging as a viable alternative to open radical cystectomy while characterized by less trauma, short recovery time and low complications. Intermediate oncologic outcomes are encouraging and comparable to those of open series. To determine the oncologic outcome long-time follow-up will be necessary.	bladder
Cultured milk, yogurt, and dairy intake in relation to bladder cancer risk in a prospective study of Swedish women and men.	BACKGROUND: Findings from epidemiologic studies of the effect of dairy foods (mainly milk) on the risk of bladder cancer have been inconsistent. OBJECTIVE: We aimed to examine the association between the intake of cultured milk and other dairy foods and the incidence of bladder cancer in a prospective, population-based cohort. DESIGN: We prospectively followed 82,002 Swedish women and men who were cancer-free and who completed a 96-item food-frequency questionnaire in 1997. Incident cases of bladder cancer were identified in the Swedish cancer registries. RESULTS: During a mean follow-up of 9.4 y, 485 participants (76 women and 409 men) were diagnosed with bladder cancer. Total dairy intake was not significantly associated with risk of bladder cancer [> or =7.0 servings/d compared with < 3.5 servings/d: multivariate rate ratio (RR) = 0.87; 95% CI: 0.66, 1.15; P for trend = 0.33]. However, a statistically significant inverse association was observed for the intake of cultured milk (sour milk and yogurt). The multivariate RRs for the highest category of cultured milk intake (> or =2 servings/d) compared with the lowest category (0 serving/d) were 0.62 (95% CI: 0.46, 0.85; P for trend = 0.006) in women and men combined, 0.55 (95% CI: 0.25, 1.22; P for trend = 0.06) in women, and 0.64 (95% CI: 0.46, 0.89; P for trend = 0.03) in men. The intake of milk or cheese was not associated with bladder cancer risk. CONCLUSION: These findings suggest that a high intake of cultured milk may lower the risk of developing bladder cancer.	bladder
Molecular pathogenesis and diagnostics of bladder cancer.	Despite elaborate characterization of the risk factors, bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. Urothelial carcinoma is now recognized as a disease of alterations in several cellular processes. The more prevalent, less aggressive, recurrent, noninvasive tumors are characterized by constitutive activation of the Ras-MAPK pathway. The less common but more aggressive invasive tumors, which have a higher mortality rate, are characterized by alterations in the p53 and retinoblastoma pathways. Several diagnostic tests have attempted to identify these molecular alterations in tumor cells exfoliated in the urine, whereas prognostic tests have tried to identify aberrations so as to predict tumor behavior and identify therapeutic targets. The future of bladder cancer patient management will rely on the use of molecular tests to reliably diagnose the presence of disease, predict individual tumor behavior, and suggest potential targeted therapeutics.	bladder
"Lower urinary tract reconstruction following a cystectomy: experience and results in 20 patients using the ""Studer"" orthotopic ileal bladder substitution."	INTRODUCTION AND OBJECTIVE: To analyze the outcome, complications and functional results in patients undergoing bladder substitution with the Studer continent urinary pouch. MATERIALS AND METHODS: At our Clinic, between January 2005 and December 2006, 20 male patients underwent a radical cystoprostatectomy followed by the Studer orthotopic bladder substitution. RESULTS: The transitional cell carcinoma was found to be the most frequent histopathological type. The distribution by grade and pathological stage showed all were high grade infiltrating tumors localized in the bladder. We observed 3 patients with neobladder-unrelated complications: one patient with a wound infection and 2 patients with a prolonged ileus. CONCLUSION: In conclusion, our results with urinary diversion are promising in patients recquiring a radical cystoprostatectomy. We believe that the Studer's orthotopic neobladder is an excellent alternative for patients suffering a radical cystectomy and offers a sufficient protection of the upper urinary tract with a low complication rate, good voiding function and continence (Tab. 1, Ref. 25). Full Text (Free, PDF) www.bmj.sk.	bladder
Evaluating inter-fractional changes in volume and position during bladder radiotherapy and the effect of volume limitation as a method of reducing the internal margin of the planning target volume.	AIMS: To quantify the inter-fractional variation in bladder volume and position during a course of bladder radiotherapy, and to assess the feasibility of reducing the planning target volume (PTV) internal margin using an empty bladder protocol. MATERIALS AND METHODS: Weekly computed tomography scans were taken immediately after micturition on 15 patients undergoing radical radiotherapy for bladder cancer. Bladder volume and positional variation were compared by co-registration of the serial computed tomography scans with the initial planning scan and a single 'full' scan at the onset of treatment for each patient. A PTV was generated on the initial planning scan using both our departmental standard of 1.5cm and a reduced 1cm isotropic internal margin around the target (whole bladder) and the relative proportion of the bladder breaching the PTV using both margins compared. RESULTS: The mean post void residual volume from the planning scan was 112cm(3) (standard deviation 42cm(3)). The mean weekly variation in bladder volume relative to the planning volume was 0-12% (standard deviation 20-34%) with no observable trends over time. No statistically significant differences were seen in the proportion of bladder breaching the 1.5 and 1cm internal margin (P=0.18). Regression analysis showed that it is possible to ensure complete coverage of the bladder with a 1cm margin, providing the volume did not exceed over 50% of the initial planning scan volume. CONCLUSION: Using an empty bladder protocol and where on-line imaging is available it is feasible to reduce the internal margin of the PTV from 1.5 to 1cm, providing the volumes do not exceed >50% of the planning scan volume.	bladder
Immune responses detected in urothelial carcinoma patients after vaccination with NY-ESO-1 protein plus BCG and GM-CSF.	Urothelial carcinoma of the bladder is a solid tumor entity for which the immunomodulatory agent Bacillus-Calmette Guerin (BCG) has been shown to have substantial efficacy with approximately 90% cure rates in select patients with superficial disease. Immune-based therapies for patients with more invasive disease do not currently exist. We previously showed that invasive urothelial carcinomas express the NY-ESO-1 tumor antigen. Here we evaluated the safety and immunogenicity of a recombinant NY-ESO-1 protein vaccine, which was administered with granulocyte macrophage colony-stimulating factor and BCG as immunologic adjuvants in a cohort of urothelial carcinoma patients. Sixty-two urothelial carcinoma patients were screened for enrollment onto the vaccine clinical trial and 6 patients met all eligibility criteria to receive vaccination. Patients with localized disease underwent surgical removal of their bladders as treatment for their disease. Tumor tissues were tested for NY-ESO-1 expression and eligible patients, shown to have NY-ESO-1 tumors, were vaccinated in the postoperative setting. Peripheral blood samples were analyzed for vaccine-induced antibody and T-cell responses. The vaccine regimen was well tolerated with only mild injection site reactions. NY-ESO-1-specific antibody responses were induced in 5/6 patients whereas CD8 T-cell responses occurred in 1/6 patients and CD4 T-cell responses were found in 6/6 patients. This study demonstrates safety and feasibility of the NY-ESO-1 recombinant protein in combination with BCG and granulocyte macrophage colony-stimulating factor to induce predominantly antibody and CD4 T-cell responses in urothelial carcinoma patients. Induction of higher frequency of CD8 T-cell responses may be possible in clinical trials implementing NY-ESO-1 vaccination in combination with other immunomodulatory agents.	bladder